Aliment. Pharmacol. Therap. (1990) 4,
43-48.
Rapid intravenous low-dosediazepam as sedation for upper gastroinfestinal endoscopy
D. G. SWAIN, D. J. ELLIS" & H. BRADBY Departments of Medicine and "Surgey, Sandwell District General Hospital, Lyndon, West Bromwich, West Midlands, UK Accepted for publication 6 October 1989
SUMMARY
One hundred patients for endoscopy, aged, between 18 and 74 years were randomly allocated to two equal groups. Group A received 10 mg diazepam intravenously rapidly over 2-4 s; Group B received diazepam intravenously over 1-2 min, titrated to provide a satisfactory level of sedation (mean dose 15.9 mg). Patient co-operation during endoscopy was similar in both groups, but one patient in Group A developed respiratory depression. Tests of psychomotor function after endoscopy showed greater impairment 30 min following injection for Group B, compared with Group A ( P < 0.02). Total or partial amnesia for endoscopy was present in 62 % of Group A, and 90% in Group B ( P < 0.005). However, postal follow-up showed that endoscopy was acceptable to 96% of Group A and 98% of Group B. Delayed sedation later in the day was reported by 26% of Group A compared with 48 % of Group B. INTRODUCTION Diazepam has been used as premedication for endoscopy for at least 15 years and is currently the most commonly used benzodiazepine in the United Kingdom for this Correspondence to: Dr D. G. Swain, Department of Geriatric Medicine, Arden Lodge Annexe, East Birmingham Hospital, Yardley Green Road, Birmingham 89 5PX,UK. 43
44
D . G . S W A I N et al
purpose.’ In view of the long half-life of diazepam (> 20 h), it is important that the minimum dose compatible with effective sedation during endoscopy is given, in order to avoid the consequences of prolonged sedation for both the patient and the operation of the endoscopy unit. The current drug data sheet recommends a dose of 0.1-0.2 mg/kg d’iazepam to be given by slow i.v. injection. A number of comparative studies have used 0.15 mg/kg diazepam given s10wly,~*~ or in a dose sufficient to sedate the patient as judged ~linically.~” There is little published work to compare the different means of administering diazepam. In the present study we compared diazepam administered as a rapid low-dose bolus with a titrated sedating dose of diazepam given slowly. MATERIALS A N D M E T H O D S A total of 100 consecutive out-patients for endoscopy, aged between 18 and 74 years, were randomly allocated to two groups. Group A received 10 mg diazepam i.v. given rapidly over 2-4 s : Group B received diazepam i.v. slowly over 1-2 min, titrated to provide a satisfactory level of sedation as judged by the endoscopist. Throughout the study, diazepam was given in the form of Diazemuls (KabiVitrum), which is an oil-in-water emulsion. Endoscopy was performed by one of two experienced endoscopists who assessed patient co-operation during the procedure on a five-point scale. Observations following endoscopy were recorded by a separate assessor. The assessor and endoscopist were blind to each others’ findings until the end of the study. Recovery from sedation was assessed by a number-connection test7 and digit substitution test,’ performed at 30 and 45 min following the procedure. The time taken was expressed as a ratio of the time taken to perform the tests prior to endoscopy. At 2 h post-procedure the patient was asked to recall sequential events, including and following administration of the baseline psychomotor tests. Total amnesia for .the procedure was defined as the patient remembering neither endoscope insertion nor withdrawal, partial amnesia as either of these, and no amnesia as remembering both insertion and withdrawal. Postal follow-up checked whether each patient would be prepared to undergo a repeat procedure, if required, using the same means of administering diazepam as with the first procedure; the letter also asked about sleeping later the same day, and whether recovery from sedation was complete the morning after endoscopy. The Mann-Whitney U-test was used for statistical analysis of ranked data, one-tailed Fisher’s exact test or t-test on proportions for nominal data, and Student’s f-test for parametric numerical data. Ridit analysis was used for comparison of assessment of patient co-operation at endoscopy.’
n.s. = not significant at 5 % level. s.d. = standard deviation.
Number of patients Male :Female Mean age (s.d.) (years) Mean weight (s.d.) (kg) Mean dose (s.d.) (mg) Mean dose/weight (s.d.) (mg/kg) Co-operation grade at endoscopy (0) Procedure abandoned (I) Mild restraint required (2) Verbal reassurance required (3) Relaxed and co-operative (4) Respiratory depression Number-connection test Ratio: time 30 min after/time before Ratio: time 45 min after/time before Digit substitution test Ratio: time 30 min after/time before Ratio: time 45 min after/time before Amnesia Total and partial No amnesia Postal questionnaire Journey home not remembered Slept in the afternoon Sleepy in the morning Repeat procedure not acceptable 45 (90%) 5 (10%)
1 (2%) 24 (48 %) 10 (20%) 1 (2%)
0 13 (26%) 13 (26%) 2 (4%)
< 0.025 n.s. n.s.
P
n.s.
P < 0.005 P < 0.001
P < 0.002 n.s. 1.20 1.00
1.03 0.95 31 (62%) 19 (38%)
P < 0.025 n.s.
n.s. (P = 0.7)
P < 0.005
n.s. n.s. ns. P < 0.005
1.40 1.10
1 7 11 30 0
50 19:31 48.2 (16.0) 67.1 (13.4) 15.9 (4.5) 0.20 (0.073)
Group B
1.22 1.07
0 4 15 30 1
0.14 (0.024)
50 27:23 48.3 (12.7) 73.3 (12.5) 10.0 (0)
Group A
Table 1. Patient characteristics, co-operation grades and recovery following sedation with diazepam given as a rapid intravenous low dose bolus (Group A), of a titrated sedating dose (Group €3)
in
46
D. G. S W A I N el al
Patients gave informed consent before entering the study, which was approved by the hospital ethics committee. The following conditions excluded patients from the study: anaemia or recent gastrointestinal bleeding, liver disease, hepatic, renal, respiratory, cardiac or brain failure ; concurrent medication with any sedative or tranquillizer, poor eyesight, non-English-speaking, and an oesophageal procedure during endoscopy.
RESULTS All patients in Group A received 10 mg of diazepam. The mean dose in Group B was 15.9 mg (s.d. 4.5 mg). The two groups were well matched for age, sex and weight (Table I). Patient co-operation was similar in the two groups. One patient in Group A, who had asymptomatic chronic airflow limitation, became centrally cyanosed with hypoventilation during endoscopy but responded quickly to removal of the endoscope and increasing the percentage of inspired oxygen. Both psychomotor tests showed significantly greater impairment at 30 min in Group B compared with Group A, but this difference had disappeared at 45 min. No patient showed retrograde amnesia. Although significantly less patients in Group A had total amnesia for the procedure, the procedure was equally acceptable to both groups, as judged by the postal responses. There was a significant difference in the degree of prolonged sedation, as manifest by sleeping in the afternoon (4-8 h following endoscopy), in Group B compared to Group A. This difference had been lost the next day, although some subjects in both groups were still sleepy the following morning (20-24 h post endoscopy). Sixteen patients in each group were taking H,-antagonists, of whom 12 in Group A and 11 in Group B were taking cimetidine: this difference was not statistically significant. Twenty-five patients in Group A and 20 in Group B took alcohol on a regular daily basis: there was no statistically significant difference between the numbers of patients in each group who drank alcohol, nor between the amounts of alcohol consumed in each group (Mann-Whitney U-test).
DISCUSSION There has been a gradual reduction in the dose of sedation given for upper gastrointestinal endoscopy in the last decade, and recent studies have suggested that sedation is required only for a few selected However, it has previously been shown that patients prefer sedation with diazepam to no sedation at all.12t13 A recent survey' showed that endoscopists in the United Kingdom prefer to sedate patients with a benzodiazepine rather than giving no sedation at all. The
RAPID LOW-DOSE DIAZEPAM FOR E N D O S C O P Y
47
best compromise is to give the lowest possible dose of sedative compatible with effective endoscopy and patient acceptability. We have found that rapid low-dose diazepam meets these requirements, and is a suitable alternative to diazepam administered slowly and titrated until sedation is judged to be adequate. Rapid low-dose diazepam led to a lower incidence of psychomotor impairment within 30 min following injection, compared with diazepam titrated to produce adequate sedation and given slowly. This would be expected to lead to a more efficient running of a busy endoscopy unit, with fewer sedated patients requiring supervision, and increased turnover of beds in the recovery area. The reduction in incidence of delayed sedation with rapid low-dose diazepam has advantages for the patient, leading to less disruption of the patient’s personal life on the day of endoscopy. The lower dose of diazepam may reduce the delay in return to work and driving a vehicle, although patients are still advised not to drive or operate machinery for at least 24 h following the endoscopy. There are cost implications of giving a lower dose of sedative. A rapid lowdose bolus of diazepam requires only one 10 mg ampoule per dose. At a cost of f 0.44 per IO-mg ampoule of diazepam in lipid emulsion, a unit that performs 2000 endoscopies in a year would save approximately f 880 annually using rapid lowdose diazepam compared to using the more traditional sedating dose of diazepam. In the current climate of financial accountability, this consideration cannot be ignored. Sedation in relation to endoscopy is not without risk.IJ4 Arterial hypoxaemia is well recognized during endo~copy~’-’~ and may lead to cardiac a r r h y t h r n i a ~ .’O~ ’ ~ ~ ~ ~ It is due to a combination of the central depressant action of the sedative causing hypoventilation, and the obstructive effect of the endoscope on the upper airway. It may be prevented by supplementary oxygen via nasal cannulae.” In this study one patient with stable chronic airflow limitation developed respiratory complications following rapid low-dose diazepam, with central cyanosis and hypoventilation. There was no immediate risk to life, and the patient responded quickly to simple measures. Although rapid low-dose diazepam was otherwise safe, its use cannot be recommended in patients with chronic airflow limitation, even if currently asymptomatic. This study has shown that rapid low-dose diazepam is comparable to higher doses of diazepam administered as recommended on the drug data sheet, and for the majority of patients it is the most appropriate means of administering diazepam for endoscopy. Further studies are required using even lower dose boluses of diazepam. ACKNOWLEDGEMENTS
We would like to thank Mr John Courtney for help in data storage and statistical analysis.
4
BAP 4
48
D. G. SWAIN et al
REFERENCES
1 Daneshmend T K, Logan R F A, Bell G D. Sedation for upper GI endoscopy-no room for complacency. The results of a national survey. Gut 1989; 30: 750-1 (Abstract.). 2. Al-Khudhairi D, Whitwam J G, McCloy R F. Comparison of midazolam and diazepam for gastroscopy. Anaesthesia 1982; 37: 1002-6. 3 Whitwam J G , Al-Khudhairi D, McCloy R F. Comparison of midazolam and diazepam in doses of comparable potency during endoscopy. Br J Anaesthesiol 1983; 55: 773-7. 4 Magni V C, Frost R A, Leung J W C, Cotton P B. A randomised comparison of midazolam and diazepam for sedation in upper gastrointestinal endoscopy. Br J Anaesthesiol 1983; 55: 1095-1101. 5. Bardhan K D, Morris P, Taylor P C, HinchIiffe R F C, Harris P A. Intravenous sedation for upper gastrointestinal endoscopy :diazepam versus midazolam. Br Med J 1984; 288 : 1046. 6 Bullimore D W, Mulley B A, Cooke P, Miloszewski K J A. Comparison of the effectiveness of midazolam and diazepam in lipid emulsion as sedation during upper gastrointestinal endoscopy. Aliment Pharmacol Therap 1987; 1: 409-14. 7 Zeegan R, Drinkwater J E , Dawson A M . Methods for measuring cerebral dysfunction in patients with liver disease. Br Med J 1970; 2 : 633-6. 8 Golden C J. The Wechsler adult intelligence scale. In : Clinical interpretation of objective psychological tests. London : Academic Press; 1979: 7-8. 9 Fleis J L. Statistical methods for rates and proportions. Chichester: John Wiley; 1973; 92-108. 10 Nichols A M , Cunningham J T . Upper endoscopy without sedation. Gastrointest Endosc 1982; 28: 140 (Abstract.). 11 Al-Atrakchi H A. Upper gastro-intestinal endoscopy without sedation: a prospective
study of 2000 examinations. Gastrointest Endosc 1989; 35 : 79-81. 12 Hawkins C F, Hoare A M. Upper gastrointestinal endoscopy with and without sedation: patients’ opinions. Br Med J 1976; 2: 20. 13 Thompson D G , Lennard-Jones JE, Evans
S J, Cowan R E, Murray R S, Wright J T. Patients appreciate premedication for endoscopy. Lancet 1980; ii: 469-70. 14 Editorial. Midazolam-is antagonism justified? Lancet 1988; ii: 140-2. 15 Atluri R, Ravry M J R. Effect of intravenous diazepam on arterial oxygen saturation levels during esophagogastroduodenoscopy. Gastrointest Endosc 1978; 24: 191 (Abstract.). 16 Rostykus P S, McDonald G B, Albert R K. Upper intestinal endoscopy induces hypoxaemia in patients with obstructive pulmonary disease. Gastroenterology 1980; 78: 488-91.
17 Lieberman D A, Wuerker C K, Katon R M. Cardiopulmonary risk of esophagogastroduodenoscopy : role of endoscope diameter and systemic sedation. Gastroenterology 1985 ; 88: 468-72. 18 Bell G D, Reeve P A, Moshiri M, et al. Intravenous midazolam: a study of the degree of oxygen saturation occuring during upper gastrointestinal endoscopy. Br J Clin Pharmacol 1987; 23 : 703-8. 19 Levy N, Abinader E. Continuous electrocardiographic monitoring with Holter Electrocardiocorder throughout all stages of gastroscopy. Am J Dig Dis 1977; 22; 1091-96. 20 Mathew P K, Ona F V, Damevski K, Wallace W A. Arrhythmias during upper gastrointestinal endoscopy. Angiology 1979; 30: 834-40. 21 Bell G D, Brown S, Morden A, Coady T, Logan R F A. Prevention of hypoxaemia during upper-gastrointestinal endoscopy by means of oxygen via nasal cannulae. Lancet 1987; i: 1022-4.
43-48.
Rapid intravenous low-dosediazepam as sedation for upper gastroinfestinal endoscopy
D. G. SWAIN, D. J. ELLIS" & H. BRADBY Departments of Medicine and "Surgey, Sandwell District General Hospital, Lyndon, West Bromwich, West Midlands, UK Accepted for publication 6 October 1989
SUMMARY
One hundred patients for endoscopy, aged, between 18 and 74 years were randomly allocated to two equal groups. Group A received 10 mg diazepam intravenously rapidly over 2-4 s; Group B received diazepam intravenously over 1-2 min, titrated to provide a satisfactory level of sedation (mean dose 15.9 mg). Patient co-operation during endoscopy was similar in both groups, but one patient in Group A developed respiratory depression. Tests of psychomotor function after endoscopy showed greater impairment 30 min following injection for Group B, compared with Group A ( P < 0.02). Total or partial amnesia for endoscopy was present in 62 % of Group A, and 90% in Group B ( P < 0.005). However, postal follow-up showed that endoscopy was acceptable to 96% of Group A and 98% of Group B. Delayed sedation later in the day was reported by 26% of Group A compared with 48 % of Group B. INTRODUCTION Diazepam has been used as premedication for endoscopy for at least 15 years and is currently the most commonly used benzodiazepine in the United Kingdom for this Correspondence to: Dr D. G. Swain, Department of Geriatric Medicine, Arden Lodge Annexe, East Birmingham Hospital, Yardley Green Road, Birmingham 89 5PX,UK. 43
44
D . G . S W A I N et al
purpose.’ In view of the long half-life of diazepam (> 20 h), it is important that the minimum dose compatible with effective sedation during endoscopy is given, in order to avoid the consequences of prolonged sedation for both the patient and the operation of the endoscopy unit. The current drug data sheet recommends a dose of 0.1-0.2 mg/kg d’iazepam to be given by slow i.v. injection. A number of comparative studies have used 0.15 mg/kg diazepam given s10wly,~*~ or in a dose sufficient to sedate the patient as judged ~linically.~” There is little published work to compare the different means of administering diazepam. In the present study we compared diazepam administered as a rapid low-dose bolus with a titrated sedating dose of diazepam given slowly. MATERIALS A N D M E T H O D S A total of 100 consecutive out-patients for endoscopy, aged between 18 and 74 years, were randomly allocated to two groups. Group A received 10 mg diazepam i.v. given rapidly over 2-4 s : Group B received diazepam i.v. slowly over 1-2 min, titrated to provide a satisfactory level of sedation as judged by the endoscopist. Throughout the study, diazepam was given in the form of Diazemuls (KabiVitrum), which is an oil-in-water emulsion. Endoscopy was performed by one of two experienced endoscopists who assessed patient co-operation during the procedure on a five-point scale. Observations following endoscopy were recorded by a separate assessor. The assessor and endoscopist were blind to each others’ findings until the end of the study. Recovery from sedation was assessed by a number-connection test7 and digit substitution test,’ performed at 30 and 45 min following the procedure. The time taken was expressed as a ratio of the time taken to perform the tests prior to endoscopy. At 2 h post-procedure the patient was asked to recall sequential events, including and following administration of the baseline psychomotor tests. Total amnesia for .the procedure was defined as the patient remembering neither endoscope insertion nor withdrawal, partial amnesia as either of these, and no amnesia as remembering both insertion and withdrawal. Postal follow-up checked whether each patient would be prepared to undergo a repeat procedure, if required, using the same means of administering diazepam as with the first procedure; the letter also asked about sleeping later the same day, and whether recovery from sedation was complete the morning after endoscopy. The Mann-Whitney U-test was used for statistical analysis of ranked data, one-tailed Fisher’s exact test or t-test on proportions for nominal data, and Student’s f-test for parametric numerical data. Ridit analysis was used for comparison of assessment of patient co-operation at endoscopy.’
n.s. = not significant at 5 % level. s.d. = standard deviation.
Number of patients Male :Female Mean age (s.d.) (years) Mean weight (s.d.) (kg) Mean dose (s.d.) (mg) Mean dose/weight (s.d.) (mg/kg) Co-operation grade at endoscopy (0) Procedure abandoned (I) Mild restraint required (2) Verbal reassurance required (3) Relaxed and co-operative (4) Respiratory depression Number-connection test Ratio: time 30 min after/time before Ratio: time 45 min after/time before Digit substitution test Ratio: time 30 min after/time before Ratio: time 45 min after/time before Amnesia Total and partial No amnesia Postal questionnaire Journey home not remembered Slept in the afternoon Sleepy in the morning Repeat procedure not acceptable 45 (90%) 5 (10%)
1 (2%) 24 (48 %) 10 (20%) 1 (2%)
0 13 (26%) 13 (26%) 2 (4%)
< 0.025 n.s. n.s.
P
n.s.
P < 0.005 P < 0.001
P < 0.002 n.s. 1.20 1.00
1.03 0.95 31 (62%) 19 (38%)
P < 0.025 n.s.
n.s. (P = 0.7)
P < 0.005
n.s. n.s. ns. P < 0.005
1.40 1.10
1 7 11 30 0
50 19:31 48.2 (16.0) 67.1 (13.4) 15.9 (4.5) 0.20 (0.073)
Group B
1.22 1.07
0 4 15 30 1
0.14 (0.024)
50 27:23 48.3 (12.7) 73.3 (12.5) 10.0 (0)
Group A
Table 1. Patient characteristics, co-operation grades and recovery following sedation with diazepam given as a rapid intravenous low dose bolus (Group A), of a titrated sedating dose (Group €3)
in
46
D. G. S W A I N el al
Patients gave informed consent before entering the study, which was approved by the hospital ethics committee. The following conditions excluded patients from the study: anaemia or recent gastrointestinal bleeding, liver disease, hepatic, renal, respiratory, cardiac or brain failure ; concurrent medication with any sedative or tranquillizer, poor eyesight, non-English-speaking, and an oesophageal procedure during endoscopy.
RESULTS All patients in Group A received 10 mg of diazepam. The mean dose in Group B was 15.9 mg (s.d. 4.5 mg). The two groups were well matched for age, sex and weight (Table I). Patient co-operation was similar in the two groups. One patient in Group A, who had asymptomatic chronic airflow limitation, became centrally cyanosed with hypoventilation during endoscopy but responded quickly to removal of the endoscope and increasing the percentage of inspired oxygen. Both psychomotor tests showed significantly greater impairment at 30 min in Group B compared with Group A, but this difference had disappeared at 45 min. No patient showed retrograde amnesia. Although significantly less patients in Group A had total amnesia for the procedure, the procedure was equally acceptable to both groups, as judged by the postal responses. There was a significant difference in the degree of prolonged sedation, as manifest by sleeping in the afternoon (4-8 h following endoscopy), in Group B compared to Group A. This difference had been lost the next day, although some subjects in both groups were still sleepy the following morning (20-24 h post endoscopy). Sixteen patients in each group were taking H,-antagonists, of whom 12 in Group A and 11 in Group B were taking cimetidine: this difference was not statistically significant. Twenty-five patients in Group A and 20 in Group B took alcohol on a regular daily basis: there was no statistically significant difference between the numbers of patients in each group who drank alcohol, nor between the amounts of alcohol consumed in each group (Mann-Whitney U-test).
DISCUSSION There has been a gradual reduction in the dose of sedation given for upper gastrointestinal endoscopy in the last decade, and recent studies have suggested that sedation is required only for a few selected However, it has previously been shown that patients prefer sedation with diazepam to no sedation at all.12t13 A recent survey' showed that endoscopists in the United Kingdom prefer to sedate patients with a benzodiazepine rather than giving no sedation at all. The
RAPID LOW-DOSE DIAZEPAM FOR E N D O S C O P Y
47
best compromise is to give the lowest possible dose of sedative compatible with effective endoscopy and patient acceptability. We have found that rapid low-dose diazepam meets these requirements, and is a suitable alternative to diazepam administered slowly and titrated until sedation is judged to be adequate. Rapid low-dose diazepam led to a lower incidence of psychomotor impairment within 30 min following injection, compared with diazepam titrated to produce adequate sedation and given slowly. This would be expected to lead to a more efficient running of a busy endoscopy unit, with fewer sedated patients requiring supervision, and increased turnover of beds in the recovery area. The reduction in incidence of delayed sedation with rapid low-dose diazepam has advantages for the patient, leading to less disruption of the patient’s personal life on the day of endoscopy. The lower dose of diazepam may reduce the delay in return to work and driving a vehicle, although patients are still advised not to drive or operate machinery for at least 24 h following the endoscopy. There are cost implications of giving a lower dose of sedative. A rapid lowdose bolus of diazepam requires only one 10 mg ampoule per dose. At a cost of f 0.44 per IO-mg ampoule of diazepam in lipid emulsion, a unit that performs 2000 endoscopies in a year would save approximately f 880 annually using rapid lowdose diazepam compared to using the more traditional sedating dose of diazepam. In the current climate of financial accountability, this consideration cannot be ignored. Sedation in relation to endoscopy is not without risk.IJ4 Arterial hypoxaemia is well recognized during endo~copy~’-’~ and may lead to cardiac a r r h y t h r n i a ~ .’O~ ’ ~ ~ ~ ~ It is due to a combination of the central depressant action of the sedative causing hypoventilation, and the obstructive effect of the endoscope on the upper airway. It may be prevented by supplementary oxygen via nasal cannulae.” In this study one patient with stable chronic airflow limitation developed respiratory complications following rapid low-dose diazepam, with central cyanosis and hypoventilation. There was no immediate risk to life, and the patient responded quickly to simple measures. Although rapid low-dose diazepam was otherwise safe, its use cannot be recommended in patients with chronic airflow limitation, even if currently asymptomatic. This study has shown that rapid low-dose diazepam is comparable to higher doses of diazepam administered as recommended on the drug data sheet, and for the majority of patients it is the most appropriate means of administering diazepam for endoscopy. Further studies are required using even lower dose boluses of diazepam. ACKNOWLEDGEMENTS
We would like to thank Mr John Courtney for help in data storage and statistical analysis.
4
BAP 4
48
D. G. SWAIN et al
REFERENCES
1 Daneshmend T K, Logan R F A, Bell G D. Sedation for upper GI endoscopy-no room for complacency. The results of a national survey. Gut 1989; 30: 750-1 (Abstract.). 2. Al-Khudhairi D, Whitwam J G, McCloy R F. Comparison of midazolam and diazepam for gastroscopy. Anaesthesia 1982; 37: 1002-6. 3 Whitwam J G , Al-Khudhairi D, McCloy R F. Comparison of midazolam and diazepam in doses of comparable potency during endoscopy. Br J Anaesthesiol 1983; 55: 773-7. 4 Magni V C, Frost R A, Leung J W C, Cotton P B. A randomised comparison of midazolam and diazepam for sedation in upper gastrointestinal endoscopy. Br J Anaesthesiol 1983; 55: 1095-1101. 5. Bardhan K D, Morris P, Taylor P C, HinchIiffe R F C, Harris P A. Intravenous sedation for upper gastrointestinal endoscopy :diazepam versus midazolam. Br Med J 1984; 288 : 1046. 6 Bullimore D W, Mulley B A, Cooke P, Miloszewski K J A. Comparison of the effectiveness of midazolam and diazepam in lipid emulsion as sedation during upper gastrointestinal endoscopy. Aliment Pharmacol Therap 1987; 1: 409-14. 7 Zeegan R, Drinkwater J E , Dawson A M . Methods for measuring cerebral dysfunction in patients with liver disease. Br Med J 1970; 2 : 633-6. 8 Golden C J. The Wechsler adult intelligence scale. In : Clinical interpretation of objective psychological tests. London : Academic Press; 1979: 7-8. 9 Fleis J L. Statistical methods for rates and proportions. Chichester: John Wiley; 1973; 92-108. 10 Nichols A M , Cunningham J T . Upper endoscopy without sedation. Gastrointest Endosc 1982; 28: 140 (Abstract.). 11 Al-Atrakchi H A. Upper gastro-intestinal endoscopy without sedation: a prospective
study of 2000 examinations. Gastrointest Endosc 1989; 35 : 79-81. 12 Hawkins C F, Hoare A M. Upper gastrointestinal endoscopy with and without sedation: patients’ opinions. Br Med J 1976; 2: 20. 13 Thompson D G , Lennard-Jones JE, Evans
S J, Cowan R E, Murray R S, Wright J T. Patients appreciate premedication for endoscopy. Lancet 1980; ii: 469-70. 14 Editorial. Midazolam-is antagonism justified? Lancet 1988; ii: 140-2. 15 Atluri R, Ravry M J R. Effect of intravenous diazepam on arterial oxygen saturation levels during esophagogastroduodenoscopy. Gastrointest Endosc 1978; 24: 191 (Abstract.). 16 Rostykus P S, McDonald G B, Albert R K. Upper intestinal endoscopy induces hypoxaemia in patients with obstructive pulmonary disease. Gastroenterology 1980; 78: 488-91.
17 Lieberman D A, Wuerker C K, Katon R M. Cardiopulmonary risk of esophagogastroduodenoscopy : role of endoscope diameter and systemic sedation. Gastroenterology 1985 ; 88: 468-72. 18 Bell G D, Reeve P A, Moshiri M, et al. Intravenous midazolam: a study of the degree of oxygen saturation occuring during upper gastrointestinal endoscopy. Br J Clin Pharmacol 1987; 23 : 703-8. 19 Levy N, Abinader E. Continuous electrocardiographic monitoring with Holter Electrocardiocorder throughout all stages of gastroscopy. Am J Dig Dis 1977; 22; 1091-96. 20 Mathew P K, Ona F V, Damevski K, Wallace W A. Arrhythmias during upper gastrointestinal endoscopy. Angiology 1979; 30: 834-40. 21 Bell G D, Brown S, Morden A, Coady T, Logan R F A. Prevention of hypoxaemia during upper-gastrointestinal endoscopy by means of oxygen via nasal cannulae. Lancet 1987; i: 1022-4.
